As a refresher, a reference listed drug (RLD) product for which sale has been discontinued or for which the firm has withdrawn its approval for commercial reasons and that was relied upon as the basis for submission of an ANDA creates a regulatory problem for firms that have approved ANDA versions or drug products with ANDAs pending at the Agency. The FDA must make a determination that the RLD, the one relied upon for ANDA submission, was not discontinued from sale or, when the NDA was withdrawn, removed from marketing for safety or efficacy (S&E) reasons.
There are two pathways that can trigger the Agency to make an official determination to that effect. First, a firm may petition the Agency to evaluate whether the withdrawn product was removed for a reason other than safety or efficacy. This pathway is usually utilized when a prospective ANDA applicant wishes to submit an ANDA for an RLD product that is no longer being marketed and is listed in the discontinued section of the Orange Book. If the FDA determines that the RLD product was withdrawn for S&E reasons, then FDA will notify the petitioner that an ANDA cannot be submitted for the drug product. The second pathway allows the FDA, on its own initiative, to review the reasons why a product was withdrawn. The FDA typically uses this pathway when there are ANDAs approved in the Orange Book that were based or an RLD that has been discontinued from sale or withdrawn.
Today, in a pre-publication notice in the Federal Register (here), the FDA, on its own initiative, reported 27 drug products that were NOT withdrawn for safety or efficacy reasons, allowing currently approved ANDAs that relied on those RLDs to remain on the market and also allowing for continued submission and acceptance of ANDAs that cite the withdrawn product as the RLD as long as they meet all current relevant legal and regulatory requirements.
The notice states:
“FDA has reviewed its records and, under § 314.161, has determined that the drug products listed were not withdrawn from sale for reasons of safety or effectiveness. Accordingly, the Agency will continue to list the drug products in the “Discontinued Drug Product List” section of the Orange Book. The “Discontinued Drug Product List” identifies, among other items, drug products that have been discontinued from marketing for reasons other than safety or effectiveness.”
It’s important to note that “If FDA determines that labeling for these drug products should be revised to meet current standards, the Agency will advise ANDA applicants to submit such labeling.” This is an important consideration as an ANDA is required to have the same labeling as that of the RLD it cites in its application with a few permitted exceptions not relevant here, but it indicates that the Agency would be responsible for informing such applicants whether any labeling updates would be required for approval. This includes, for example, any new warnings, format labeling changes, or the addition of any other information that the Agency deems appropriate for the continued marketing of the product.
